This application represents the third competitive renewal for our Training Program that prepares young investigators to conduct research in age-related neurodegenerative diseases. Through an intensive program of education, research training, and mentorship, these trainees will become independent investigators who will pursue careers to further our understanding of the etiology, pathogenesis, diagnosis, and treatment of these diseases. Trainees will include predoctoral PhD and MD/PhD students in neuroscience and related disciplines as well as postdoctoral PhD and MD scientists with prior training in the neurosciences, pharmacology, neuropathology, psychiatry, and gerontology. Predoctoral trainees will be given a solid background in neuroscience and related disciplines, including exposure to many diverse techniques, methods, and approaches in the setting of a research intensive academic medical center and university with a highly interactive group of trainers. They will then select a mentor from a pool of seventeen trainers with wide-ranging interests and complementary expertise. Postdoctoral trainees will participate actively in investigations underway in the laboratory of their choosing. Joint supervision of a trainee by more than one trainer will be encouraged; and physician trainees will also have the opportunity to pursue patient oriented research. Penn has an extensive didactive program in neurosciences, pharmacology, and other basic sciences that can be individually tailored to the needs of each trainee as a supplement to their core research training. Each trainee will undertake an independent project that will provide experience in the design and analysis of experiments and in the presentation and publication of results. Trainees will also participate in weekly research seminars that promote a constant interchange among trainees and trainers and encourage collaboration.